Short-term PI3K Inhibition Prevents Breast Cancer in Preclinical Models
Abstract
Antiestrogen medication is the only chemoprevention currently available for women at a high risk of developing breast cancer; however, antiestrogen therapy requires years to achieve efficacy and has adverse side effects. Therefore, it is important to develop an efficacious chemoprevention strategy that requires only a short course of treatment. PIK3CA is commonly activated in breast atypical hyperplasia, the known precancerous precursor of breast cancer. Targeting PI3K signaling in these precancerous lesions may offer a new strategy for chemoprevention. Here, we first established a mouse model that mimics the progression from precancerous lesions to breast cancer. Next, we demonstrated that a short-course prophylactic treatment with the clinically approved PI3K inhibitor alpelisib slowed early lesion expansion and prevented cancer formation in this model. Furthermore, we showed that alpelisib suppressed ex vivo expansion of patient-derived atypical hyperplasia. Together, these data indicate that the progression of precancerous breast lesions heavily depends on the PI3K signaling, and that prophylactic targeting of PI3K activity can prevent breast cancer.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 04, 2022
- Source ID
- 10.1158/1940-6207.capr-22-0275
Entities
People
- Adelaide Ij Young
- Ahmed Atef Ibrahim
- Amy T. Ku
- Bryant Lee McCue
- Chandandeep Nagi
- Fariba Behbod
- George Miles
- LaTerrica Williams
- Meng Lin
- Weiyu Jiang
- Wen Bu
- Yi Li
Organizations
- Baylor College of Medicine
- Cancer Prevention and Research Institute of Texas
- Congressionally Directed Medical Research Programs
- National Institutes of Health
- University of Kansas